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SOX2 Variant Resulting in Hypogonadotropic Hypogonadism, Learning Difficulties, and Ear (Rather Than Eye) Anomalies

Year: 2025

Type: article

Abstract: A 15-year-old female individual presented with primary amenorrhea and absence of pubertal signs. Her hormonal profile revealed isolated hypogonadotropic hypogonadism (IHH) with low levels of luteinizing hormone (LH), estradiol, and follicle-stimulating hormone (FSH), with a confirmatory luteinizing hormone–releasing hormone (LHRH) stimulation test. She has a background of global developmental delay and bilateral hearing loss, with computed tomography (CT) findings of an absent right incus lenticular process and a dilated right vestibule. Genetic testing revealed a heterozygous pathogenic variant c.152G>A (p.Trp51*) in the SOX2 gene. SOX2 (sex-determining region Y-box 2) is a transcription factor critical for early pituitary and hypothalamic development. However, the phenotype associated with SOX2 pathogenic variants remains incompletely defined due to its rarity and wide phenotypic variability. Our case uniquely highlights temporal bone anomalies and a comprehensive pituitary function workup, which may contribute to a clearer understanding of SOX2-related phenotypic presentations. This case underscores the need to consider SOX2 pathogenic variants in the genetic evaluation of IHH, even in the absence of ocular abnormalities.

Source: JCEM Case Reports

DOI: 10.1210/jcemcr/luaf126

Authors: Wen Qi Cher, Daniel Chan

Institutions: SingHealth, KK Women's and Children's Hospital, National University of Singapore, Duke-NUS Medical School

Language: English

Topic: Hypothalamic control of reproductive hormones

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $930